Low Dose Chemotherapy Versus Best Supportive Care in Progressive Pediatric Malignancies

NCT ID: NCT01858571

Last Updated: 2017-01-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2017-01-31

Brief Summary

Many of the pediatric malignancies are not curable on progression on front line or 2nd line chemotherapy. Further therapy with conventional drugs imposes many side effects and decreases the QOL. The usual therapy offered to such patients is best supportive care.

Metronomic chemotherapy can induce tumor stabilization or tumor responses in patients with cancer that are refractory or have relapsed after conventional chemotherapy. Whether metronomic therapy is better than best supportive care is not known. In order to do so, a study is required which may compare metronomic therapy with a placebo therapy on PFS and QOL in relapsed refractory cases of pediatric solid tumors who have failed at least two lines of chemotherapy.

HYPOTHESIS

The investigators hypothesize that metronomic chemotherapy in progressive pediatric malignancy will improve PFS and QOL. If validated, then this form for therapy will be an option for both the patients and the clinicians, who are left with just an option of best supportive care in such situations of progressive pediatric cancers despite multiple lines of chemotherapy.

Detailed Description

Many of the pediatric malignancies are not curable on progression on front line or 2nd line chemotherapy. Further therapy with conventional drugs imposes many side effects and decreases the QOL. The usual therapy offered to such patients is best supportive care.

Metronomic chemotherapy can induce tumor stabilization or tumor responses in patients with cancer that are refractory or have relapsed after conventional chemotherapy. Whether metronomic therapy is better than best supportive care is not known. In order to do so, a study is required which may compare metronomic therapy with a placebo therapy on PFS and QOL in relapsed refractory cases of pediatric solid tumors who have failed at least two lines of chemotherapy.

It will be double blind randomized study. One group will receive metronomic therapy along with best supportive care and other will receive placebo and best supportive care.

The treatment will be continued till progression is documented. Metronomic chemotherapy schedule : Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size.

Cycle A

• Daily oral Thalidomide (at 3mg/kg)
• Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
• Daily oral Etoposide (50 mg/m2/d) Cycle B
• Daily oral Thalidomide (at 3mg/kg)
• Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
• Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days

Placebo: Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration)

• Capsules of same size and color as used in metronomic therapy Best supportive care
• Management of pain as per WHO standard for pain management

The dose of medications in capsules have to be rounded off to the nearest capsule size. Instead of rounding off on the daily dose, the total dose over the week would be calculated and rounded off and divided over 5-6 days in a week. This is being done so as to prevent any extra dosing.

If any grade 3-4 toxicity occurs in the first course, then the dose for chemotherapy would be reduced in the subsequent course by 20%.

Conditions

Malignant Childhood Neoplasm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Low dose chemotherapy

Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size.

Cycle A

• Daily oral Thalidomide (at 3mg/kg)
• Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
• Daily oral Etoposide (50 mg/m2/d)

Cycle B

• Daily oral Thalidomide (at 3mg/kg)
• Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
• Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days

Group Type: EXPERIMENTAL

Low dose chemotherapy

Intervention Type: DRUG

Metronomic chemotherapy schedule : Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size.

Cycle A

• Daily oral Thalidomide (at 3mg/kg)
• Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
• Daily oral Etoposide (50 mg/m2/d)

Cycle B

• Daily oral Thalidomide (at 3mg/kg)
• Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
• Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days

Best supportive care

Placebo: Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration)

• Capsules of same size and color as used in metronomic therapy Best supportive care
• Management of pain as per WHO standard for pain management

Group Type: PLACEBO_COMPARATOR

Low dose chemotherapy

Intervention Type: DRUG

Metronomic chemotherapy schedule : Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size.

Cycle A

• Daily oral Thalidomide (at 3mg/kg)
• Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
• Daily oral Etoposide (50 mg/m2/d)

Cycle B

• Daily oral Thalidomide (at 3mg/kg)
• Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
• Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days

Interventions

Low dose chemotherapy

Metronomic chemotherapy schedule : Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size.

Cycle A

• Daily oral Thalidomide (at 3mg/kg)
• Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
• Daily oral Etoposide (50 mg/m2/d)

Cycle B

• Daily oral Thalidomide (at 3mg/kg)
• Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
• Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days

Intervention Type: DRUG

Other Intervention Names

•Thalidomide •Celecoxib •Etoposide •Cyclophosphamide

Eligibility Criteria

Inclusion Criteria

1. Refractory/Progressive non hematopoietic extracranial solid tumors following treatment with at least 2 lines of chemotherapy.

2. ECOG performance status (<=3)(at least patients ambulating with crutches or on wheel chair)

3. Age: 5-18 years

4. Recovered from all acute toxic effects of earlier therapy

5. Absolute neutrophil count > 1X 109/L

6. Absolute platelet count > 75 x 109/L

7. Normal renal functions

8. Serum bilirubin <1.5 times the upper limit of normal, and the serum aspartate aminotransferase and alanine aminotransferase < 5 times the upper limit of normal.

Exclusion Criteria

1. Uncontrolled concurrent illness or active infection

2. Positive serology for human immunodeficiency.

3. Unable to swallow oral medication

4. Pregnant and breast-feeding

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

All India Institute of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Sameer Bakhshi

Additional Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sameer Bakhshi, MD

Role: PRINCIPAL_INVESTIGATOR

All India Institute of Medical Sciences

Locations

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, India

Countries

India

References

Pramanik R, Agarwala S, Sreenivas V, Dhawan D, Bakhshi S. Quality of life in paediatric solid tumours: a randomised study of metronomic chemotherapy versus placebo. BMJ Support Palliat Care. 2023 Jun;13(2):234-237. doi: 10.1136/bmjspcare-2020-002731. Epub 2021 Jan 19.

Reference Type: DERIVED

PMID: 33468507 (View on PubMed)

Pramanik R, Agarwala S, Gupta YK, Thulkar S, Vishnubhatla S, Batra A, Dhawan D, Bakhshi S. Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors: A Randomized Clinical Trial. JAMA Oncol. 2017 Sep 1;3(9):1222-1227. doi: 10.1001/jamaoncol.2017.0324.

Reference Type: DERIVED

PMID: 28384657 (View on PubMed)

Other Identifiers

IEC/NP-63/2013

Identifier Type: -

Identifier Source: org_study_id